1. Field of the Invention
The present invention relates to the use of nucleic acids such as deoxyribonucleic acid and ribonucleic acid (hereinafter collectively referred to as "NA") as a filter for removing environmental hazards that otherwise would pose a threat to the genetic material of living organisms such as plants and animals, including humans. More particularly, the present invention relates to a method of use of NA as a sunlight or artificial UV light filter to selectively remove nucleic acid-damaging ultraviolet radiation, for example, from sunlight or artificial UV source, before it contacts a living organism. Even more particularly, the present invention relates to NA-containing compositions and articles which form an ultraviolet radiation-absorbing layer between the sun and living organisms where the layer specifically blocks nucleic acid-damaging ultraviolet radiation before it contacts a living organism.
2. Background of the Invention
One of the major causes of cancer is the alteration of the cellular genome. Environmental hazards that specifically react with nucleic acids are a major cause of these genetic alterations, and hence a major cause of cancer in both plants and animals. Typical environmental hazards that have nucleic acid-damaging capabilities include, inter alia, ultraviolet radiation, ionizing radiation, and environmental chemicals that display either nucleic acid intercalating activity or the ability to form adducts with nucleic acids.
Exposure to ultraviolet radiation from the sun is generally believed to be the major cause of non-melanoma skin cancers and a major cause of malignant melanoma skin cancers (Moan and Dahlback, Br. J. Cancer 65:916-921, 1992). Rates of both non-melanoma and malignant melanoma skin cancers have increased dramatically in recent years. For example, during the period between 1957 and 1984 in Norway, the incidence of cutaneous malignant melanoma increased by 350% for men and 440% for women. According to a recent U.S. federal survey taken between 1977-1988, about 500,000 basal-cell carcinomas and 100,000 squamous-cell carcinomas occur annually. Other, smaller surveys suggest the incidence may have increased by as much as 65% since 1980. (Preston and Stern, New England J. Med., 327:1649-1662, 1992). Scientists have linked the recent increase in skin cancer with the decrease in the Earth's protective ozone layer, a layer that normally filters out much of the nucleotide damaging ultraviolet radiation in sunlight. As the Earth's protective ozone layer continues to decrease, the earth's surface is exposed to increasingly higher levels of nucleic acid-damaging ultraviolet radiation from the sun. Ozone depletion may seriously impact such important biological end-points as skin cancer, cataracts, the immune system, crop yields, and oceanic phytoplankton (Coohill, Photochemistry and Photobio., 54:859-870, 1991). Scientists believe that this increased irradiation will especially lead to a related increase the incidence of sunlight-induced skin cancer. (Kelfkens G., etc. Photochem. Photobiol., 52(4):819-23, 1990). Henriksen predicted a two percent increase in overall skin cancer for each one percent depletion of stratospheric ozone. (Henriksen T., Photochem. Photobiol. 51(5):579-82, 1990).
Currently, in response to the threat of exposure to harmful ultraviolet radiation from the sun, people are advised to avoid excessive exposure to sunlight, and when in the sun, to wear sunscreens. The shortcomings of these actions are many fold, including their limitation to humans, as opposed to all other living creatures, as well as numerous problems inherent in existing sunscreen technology.
A more desired response to the global threat of increased exposure to nucleic acid-damaging ultraviolet radiation would provide protection for all living creatures, not merely humans. The present invention affords such protection.
Existing topical sunscreens fall within one of two categories: (1) chemical, and (2) physical sunscreens. Physical sunscreens operate by blocking out nearly all wavelengths of sunlight (290-760 nm). They are typically applied in an opaque cream or lotion containing particulate ingredients that do not selectively absorb ultraviolet radiation, but when applied as a thin film, primarily reflect and scatter sunlight. Common ingredients in physical sunscreens include titanium dioxide, zinc oxide and talc.
Because they completely block all sunlight, known physical sunscreens prevent the beneficial effects of sunlight upon the skin. For example, physical sunscreens block the wavelengths of sunlight that are essential for the skin to convert 7-dehydro-cholesterol into vitamin D.sub.3 (Matsuoka et.al., Arch. Dermatol. 124:1802-1804, 1988) and block sunlight required for the photoactivation of a protein called photolyase which is involved in cellular DNA repair mechanism (Rupert, C. S., J.Gen.Physiol. 45:725-741, 1962). Physical sunscreens also prevent the often desired "tanning" of the skin which would otherwise occur upon exposure to moderate amounts of sunlight. Further, physical sunscreen formulations are cosmetically unpleasing, unacceptable to many patients, and messy to use.
Chemical sunscreens contain one or more ultraviolet-absorbing chemicals which are generally colorless, and upon application of a thin and invisible film, act as filters to selectively prevent certain wavelengths of ultraviolet light from reaching the cells of the epidermis. However, since chemical sunscreens are non-natural molecules, their molecular structures are quite different from the nucleic acid molecules which are the direct target for ultraviolet light-induced damage to living organisms (Ananthaswamy and Pierceall, Photochem and Photobiol., 52(6):1118-1136, 1990). Also, due to a lack of understanding of the photochemistry of nucleic acids, whether or not chemical sunscreens protect living organisms from skin cancer is still an unresolved controversy (Gurish, J. Invest. Dermatol., 76:246-251, 1981; Knowland, FEBS Letters, 324:308-313, 1993; Thompson, The New England J. of Med., 328:1147-1151, 1993). Further, the radiation that is blocked out by known chemical sunscreens often includes frequencies of sunlight that are beneficial to the body such as the wavelengths of ultraviolet light that are necessary for the body to produce vitamin D.
Most commercial sunscreens contain at least one each of two different types of chemicals: UV-A-absorbing chemicals and UV-B-absorbing chemicals. UV-A-absorbing chemicals absorb ultraviolet radiation in the range of 320-400 nm. UV-B-absorbing chemicals absorb ultraviolet radiation in the range of 290-320 nm. The wavelength range of UV-A and UV-B (290-400 nm) includes the frequencies of ultraviolet light that cause sunburn (290-350 nm), however, it also includes beneficial wavelengths of ultraviolet light such as those that are necessary for the skin's production of vitamin D.sub.3 (290-315 nm) and also those required for repair of pyrimidine dimers (320-600 nm) (Spikes, J. D., In: Experimental and Clinical Photoimmunology, Daynes and Spikes (eds.), CRC Press, Boca Raton (1983); Chiang and Rupert, Photochem. Photobiol., 30:525-528, 1979; Hanawalt and Haynes, Scientific American, 216:36, 1967).
UV-absorbing chemicals include para-aminobenzoic acid (PABA) and esters thereof, benzophenones, and cinnemates which selectively absorb and screen sunburn-producing UV radiation (290-320 nm). However, sunscreening formulations containing these chemicals can cause selective burning (smarting), contact dermatitis, and allergic contact dermatitis. (Kaidbey et al., J. Soc. Cosmet. Chem. 29:525-536, 1978; Fisher, AA, Arch. Dermatol., 113: 1288-1300, 1977; Toby-Mathias et al., Arch Dermatol., 114:1665-1666, 1978). Further, synthetic procedures for producing UV-absorbing chemicals may introduce contaminants into the preparation, some which may be carcinogenic. For example, urocranic acid was commercially available as a sunscreen to block UV-B, but was removed from the market because of its link to skin cancer (Consumer Reports, June 1991, p. 406). Chemical sunscreens may mutate on exposure to sunlight, the mutagen being carcinogenic. Indeed, studies suggest that chemical sunscreens might encourage rather than prevent sunlight-related cancers (Knowland et al., FEBS Letters, 324:309-313, 1993).
Further, the sun protection factor (SPF) rating used to quantitate protection offered by a commercial sunscreen product is based upon erythema, a morphological criteria that is not directly related to quantitation of genetic hazard protection. The SPF rating may be more harmful than useful. Those who purchase and use a sunscreen with a high SPF expect the sunscreen to protect them from genetic hazard UV radiation. With a false sense of security, they may spend a greater amount of time exposed to UV radiation, while the sunscreen may not provide adequate protection. (Young, British J. of Dermatology, 122, Supplement 35:111-114, 1990; Young, Pigment Cell Research, 1:350-4, 1988). The SPF rating is not directly related in any way to UV-induced DNA damage. The SPF standard is based upon erythema, or redness caused by UV exposure.
The wavelengths of light absorbed by the various chemical sunscreens differs with the compounds used. Because the specific wavelengths responsible for UV-induced DNA damage are not fully understood, a non-target compound cannot be certain to be an effective filter.
It would be of great utility to provide a natural genetic hazard UV radiation filter which could selectively and specifically eliminate genetic-hazard inducing UV radiation.